Is DCDC2 p.Glu317Gln (c.949G>C) pathogenic?

DCDC2 p.Glu317Gln (c.949G>C) is classified Uncertain significance in DCDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-04). AlphaMissense: likely benign (0.0987); Absent from gnomAD v4.1; Associated with nephronophthisis 19.

What condition is associated with DCDC2 p.Glu317Gln (c.949G>C)?

DCDC2 p.Glu317Gln (c.949G>C) is associated with nephronophthisis 19, autosomal recessive nonsyndromic hearing loss 66, isolated neonatal sclerosing cholangitis (ClinVar).

How common is DCDC2 p.Glu317Gln (c.949G>C) in the general population?

DCDC2 p.Glu317Gln (c.949G>C) is absent from gnomAD v4.1 (gnomAD).

How is Nephronophthisis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DCDC2 p.Glu317Gln (c.949G>C)?

AlphaMissense predicts likely benign (score 0.0987) — an in-silico prediction, not a clinical call.

DCDC2 p.Glu317Gln

c.949G>C · VCV3593410

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephronophthisis 19

Computational evidence

Protein change
AlphaMissense	0.0987	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -7.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 183 kb · p 0.62 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DCDC2
Protein: p.Glu317Gln
Coding: c.949G>C
MANE Select: NM_016356
Type: single nucleotide variant
Location: chr6:24205076 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB
Residue 317: a UniProt-annotated variant site (in nsc); the 'disordered' region

Full DCDC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephronophthisis 19 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive nonsyndromic hearing loss 66 isolated neonatal sclerosing cholangitis

For Nephronophthisis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Finland)

Similar variants

DCDC2 c.294-2A>G Pathogenic ★★ same condition
DCDC2 c.349-2A>G Pathogenic ★★ same condition
DCDC2 c.705-2A>G Pathogenic ★★ same condition
DCDC2 p.Leu297Ter Pathogenic ★★ same condition
DCDC2 p.Met1Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
DCDC2 p.Ser128Ter Pathogenic/Likely pathogenic ★★ same condition
DCDC2 p.Ala384Gly Uncertain significance ★★ ⚠ same condition
DCDC2 p.Ala93Asp Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dcdc2-p-glu317gln (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown